HOX antisense intergenic RNA (HOTAIR) an extended non-coding RNA plays an

HOX antisense intergenic RNA (HOTAIR) an extended non-coding RNA plays an important role in the development of many types of cancers. low HOTAIR expression overall survival and event-free survival of patients with high HOTAIR expression was significantly reduced. In addition the expression of downstream genes in the HOTAIR signaling pathway including EZH2 LSD1 DNMT3A and DNMT3B was significantly increased in AL patients and showed a significant positive correlation with high expression of HOTAIR (P<0.05). In conclusion HOTAIR was closely related with a poor prognosis in AL patients. It may be involved in the development AMN-107 of leukemia by mediating methylation of DNA and histones. (8) were the first to identify an lncRNA regulating gene expression in at the HOXC gene locus on chromosome 12. The lncRNA is usually involved in regulation of HOX gene clusters located on different chromosomes rather than (9) subsequently found that the expression level of HOTAIR in breast malignancy metastases was significantly higher than in main breast cancer and normal breast tissues and that the high expression of HOTAIR was associated with metastasis and a poor prognosis for patients. An additional two studies on breast cancer AMN-107 reached comparable conclusions (10 11 Further studies showed that expression levels of HOTAIR were also significantly increased in colorectal malignancy (12) hepatocellular carcinoma (13) lung (14) pancreatic (15) and nasopharyngeal malignancy (16) and other malignant tumors and metastases. Furthermore malignancy patients with high HOTAIR expression had lower survival rates and higher recurrence rates (17). These studies suggested AMN-107 that HOTAIR was involved in tumorigenesis and experienced significant clinical importance. Studies have shown that HOTAIR epigenetically regulates gene expression acting as a scaffold for protein complexes in both PRC2 and LSD1-mediated target gene silencing. PRC2 a member of PcG family consists of the core elements EZH2 EED and SUZ12 as well as histone binding protein RbAp46 and PHFl. EZH2 is an important subunit with catalytic activity with a highly conserved SET structural domain name that methylates the 9th and 27th lysine in the nucleosome histone H3 thereby inhibiting hundreds of genes. These include genes involved in cell growth differentiation tumor metastasis and expression of related genes. SUZ12 and EED maintain the stability of the complex and are essential components in the catalysis of PRC2 complexes (18). The LSD1 complex is usually comprised of LSD1 REST CoREST HDAC1-2 BHC80 and BRAF35 (19 20 LSD1 removes the methyl groups on H3K4me1/2 and H3K9me1/2 resulting in a single methyl group or no methyl group thereby regulating transcription of downstream genes (21). REST as a DNA-binding protein is usually involved AMN-107 in localization of the LSD1 complex to the correct genomic location. CoREST can bind with nucleosomes and recruit LSD1 to demethylate H3K4. Together these proteins cooperatively inhibit transcription. Although HOTAIR has been implicated in the onset of a variety of tumors its role in hematological tumor formation remains unclear. To date Rabbit polyclonal to Rex1 its significance in terms of diagnosis and prognosis in leukemia has not been extensively analyzed. HOTAIR functions as a scaffold for histone modification complexes and is involved in epigenetic gene regulation (22). The present study aimed to examine whether expression of DNA AMN-107 methyltransferases and histone methyltransferases in leukemia patients was modulated by HOTAIR and whether HOTAIR could act as a diagnostic/prognostic marker for leukemia. Materials and methods Patients Ninety-six bone marrow cell samples were collected from patients diagnosed with leukemia and treated at the Affiliated Union Hospital of Fujian Medical University or college between October 2011 and February 2015. Patients included 56 males and 40 females between the ages of 14 and 84. Seventy-three cases were acute myelogenous leukemia and 23 cases were acute lymphoblastic leukemia. Eighty bone marrow samples from bone marrow donors and patients with non-hematologic malignancies were studied as controls. All specimens were obtained with approval from your Medical Ethics Committee and the patients informed consent. Inclusion criteria were as follows: i) diagnosis and classification of AL according to the French-American-British (FAB) classification criteria; ii) confirmation of the AL.